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1.
AIDS Res Ther ; 19(1): 61, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36471425

RESUMO

BACKGROUND: There are more than 7,800 people living with human immunodeficiency virus (HIV) in Victoria, Australia. Crucial in maximising the individual and population level benefits from antiretroviral therapy (ART) is understanding how to achieve patient retention in care and the factors that drive it. This study was an expansion of a 2015 assessment of HIV-care retention in Victoria, which sought out to determine whether the inclusion of a broader range of HIV-healthcare sites would yield more accurate estimates of retention in HIV-care. We aimed to improve our understanding of HIV-care retention in Victoria, Australia, identify people living with HIV (PLHIV) with unknown outcomes, and attempt to re-engage PLHIV in care. METHODS: A network of 15 HIV-care sites was established in Victoria, Australia across diverse care settings which ranged from low-caseload rural sites to high-caseload metropolitan GP clinics and hospitals. Individuals who had an HIV viral load (VL) performed in both calendar years of 2016 and 2017 were classified as retained in care. Individuals with a VL test in 2016 but not in 2017 were considered to potentially have unknown outcomes as they may have been receiving care elsewhere, have disengaged from care or died. For this group, an intervention of cross-referencing partially de-identified data between healthcare sites, and contact tracing individuals who still had unknown outcomes was performed. RESULTS: For 5223 individuals considered to be retained in care across 15 healthcare sites in the study period, 49 had unconfirmed transfers of care to an alternative provider and 79 had unknown outcomes. After the intervention, the number of unconfirmed care transfers was reduced to 17 and unknown outcomes reduced to 51. These changes were largely attributed to people being reclassified as confirmed transfers of care. Retention in care estimates that did not include the patient outcome of confirmed transfer of care ranged from 76.2 to 95.8% and did not alter with the intervention. However, retention in care estimates which considered confirmed transfers and those that re-entered care at a new site as retained in care significantly increased across five of the sites with estimates ranging from 80.9 to 98.3% pre-intervention to 83.3-100% post-intervention. Individuals whose outcomes remained unknown post-intervention were more often men who have sex with men (MSM) when compared to other categories (person who injects drugs (PWID), combined PWID/MSM, men who identify as heterosexual or unknown) (74.5% vs. 53.5%, [p = 0.06]) and receiving ART at their last HIV-care visit (84.3% vs. 67.8% [p = 0.09]). CONCLUSION: This study confirmed high retention in HIV-care and low numbers of people disengaged from HIV-care in Victoria. This was demonstrated across a larger number of sites with varying models of care than a prior assessment in 2015. These data align with national and state targets aiming for 95% of PLHIV retained in HIV-care.


Assuntos
Infecções por HIV , Retenção nos Cuidados , Minorias Sexuais e de Gênero , Abuso de Substâncias por Via Intravenosa , Masculino , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Homossexualidade Masculina
2.
Sex Health ; 16(3): 282-288, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31167698

RESUMO

Background Women comprise ~10% of people living with HIV in Australia, so are often underrepresented in research. METHODS: This study invited clinicians providing care to women living with HIV to complete an anonymous survey containing questions related to four key areas: HIV (including diagnosis, treatment and virological outcomes), reproductive health (including sexual activity, contraception, pregnancy and outcomes) and linkage and retention in care. RESULTS: In total, 484 surveys were received, with responses from all states and territories. Most women living with HIV in Australia are on treatment (>90%) and virologically suppressed (>90% have a viral load <50 copies mL-1). Almost 75% of women have had at least one switch in treatment (with toxicity almost as common as simplification as the indication). Treatment interruption is also relatively common, but is more likely the longer a woman has been diagnosed, if she is on benefits (P = 0.007) and is the primary carer of children without a partner (P = 0.001). In Australia, women living with HIV are a diverse heterogeneous group, with over 70 different countries of birth and almost half speaking a language other than English at home. Mental health diagnosis was the most common co-morbid condition identified. A total of 21% of women were post-menopausal, with 42% reporting symptoms to their healthcare provider, but only 17% were receiving treatment for symptoms attributed to menopause. CONCLUSIONS: As well as strategies to support women vulnerable to treatment interruption, important areas for future investment in research and clinical care include co-morbid mental health and menopause symptoms and treatment.


Assuntos
Anticoncepção , Substituição de Medicamentos , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Retenção nos Cuidados , Comportamento Sexual , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Comorbidade , Feminino , Infecções por HIV/epidemiologia , Humanos , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Pós-Menopausa , Gravidez , Resultado da Gravidez , Inquéritos e Questionários , Carga Viral , Adulto Jovem
3.
Clin Infect Dis ; 66(1): 89-94, 2018 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-29020213

RESUMO

Background: Central nervous system (CNS) histoplasmosis is a life-threatening condition and represents a diagnostic and therapeutic challenge. Isolation of Histoplasma capsulatum from cerebrospinal fluid (CSF) or brain tissue is diagnostic; however, culture is insensitive and slow growth may result in significant treatment delay. We performed a retrospective multicenter study to evaluate the sensitivity and specificity of a new anti-Histoplasma antibody enzyme immunoassay (EIA) for the detection of IgG and IgM antibody in the CSF for diagnosis of CNS histoplasmosis, the primary objective of the study. The secondary objective was to determine the effect of improvements in the Histoplasma galactomannan antigen detection EIA on the diagnosis of Histoplasma meningitis. Methods: Residual CSF specimens from patients with Histoplasma meningitis and controls were tested for Histoplasma antigen and anti-Histoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody using assays developed at MiraVista Diagnostics. Results: A total of 50 cases and 157 controls were evaluated. Fifty percent of patients with CNS histoplasmosis were immunocompromised, 14% had other medical conditions, and 36% were healthy. Histoplasma antigen was detected in CSF in 78% of cases and the specificity was 97%. Anti-Histoplasma IgG or IgM antibody was detected in 82% of cases and the specificity was 93%. The sensitivity of detection of antibody by currently available serologic testing including immunodiffusion and complement fixation was 51% and the specificity was 96%. Testing for both CSF antigen and antibody by EIA was the most sensitive approach, detecting 98% of cases. Conclusions: Testing CSF for anti-Histoplasma IgG and IgM antibody complements antigen detection and improves the sensitivity for diagnosis of Histoplasma meningitis.


Assuntos
Anticorpos Antifúngicos/líquido cefalorraquidiano , Antígenos de Fungos/líquido cefalorraquidiano , Histoplasmose/diagnóstico , Técnicas Imunoenzimáticas/métodos , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina M/líquido cefalorraquidiano , Meningite Fúngica/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Líquido Cefalorraquidiano/imunologia , Líquido Cefalorraquidiano/microbiologia , Criança , Pré-Escolar , Testes Diagnósticos de Rotina/métodos , Feminino , Galactose/análogos & derivados , Humanos , Lactente , Masculino , Mananas/líquido cefalorraquidiano , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
4.
J Clin Microbiol ; 56(10)2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30021828

RESUMO

The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-ß-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF BDG level was 85 pg/ml for cases, compared to <31 pg/ml for all controls (P < 0.05) and 82 pg/ml for controls with other causes of fungal meningitis (P = 0.27). The sensitivity for detection of BDG in CSF was 53.2%, whereas the specificity was 86.9% versus all controls and 46% versus other CNS fungal infections. CSF BDG levels of ≥80 pg/ml are neither sensitive nor specific to support a diagnosis of Histoplasma meningitis.


Assuntos
Técnicas de Laboratório Clínico/métodos , Histoplasmose/diagnóstico , beta-Glucanas/líquido cefalorraquidiano , Adulto , Biomarcadores/líquido cefalorraquidiano , Histoplasma/isolamento & purificação , Histoplasma/metabolismo , Histoplasmose/líquido cefalorraquidiano , Humanos , Meningite Fúngica/líquido cefalorraquidiano , Meningite Fúngica/diagnóstico , Meningite Fúngica/microbiologia , Proteoglicanas , Curva ROC , Kit de Reagentes para Diagnóstico
5.
Intern Med J ; 47(12): 1433-1436, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29224209

RESUMO

BACKGROUND: Currently, treatment of latent tuberculosis infection (LTBI) in Australia consists most commonly of a 9-month course of isoniazid (9H). A 3-month course of weekly isoniazid and rifapentine (3HP) has been shown to be as effective as 9 months of daily isoniazid, and associated with less hepatotoxicity; however, rifapentine is not currently available in Australia. Introduction of this regimen would have apparent advantages for people with LTBI in Victoria by safely shortening duration of LTBI therapy. However, the cost benefit of this new therapeutic approach is uncertain. AIM: Cost-analysis of standard and short-course therapy for LTBI in an Australian context. METHODS: Single-centre randomised controlled trial conducted between December 2013-March 2016. Participants underwent 1:1 randomisation to either a 9-month course of daily isoniazid or a 12-week course of weekly isoniazid and rifapentine. The primary outcome measure was total healthcare system costs (in Australian dollars; AUD) per completed course of LTBI therapy. Secondary cost analyses were performed to consider varying assumptions regarding commercial cost of rifapentine. RESULTS: Overall, 34 of 40 (85%) participants in the 9H group and 36/40 (90%) in the 3HR group completed therapy. One patient in the 3HP group was hospitalised for a febrile illness; no hospitalisations were recorded in the 9H group. The cost per completed course of 9H was 601 AUD, while that of 3HP was significantly lower at 511 AUD (P < 0.01). CONCLUSIONS: This study provides cost analysis evidence to support the use of 3HP for the treatment of LTBI in Australia.


Assuntos
Antituberculosos/economia , Análise Custo-Benefício/métodos , Erradicação de Doenças/métodos , Isoniazida/economia , Tuberculose Latente/economia , Rifampina/análogos & derivados , Adolescente , Adulto , Idoso , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/economia , Antituberculosos/administração & dosagem , Austrália , Esquema de Medicação , Feminino , Humanos , Isoniazida/administração & dosagem , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Estudos Prospectivos , Rifampina/administração & dosagem , Rifampina/economia , Autoadministração , Adulto Jovem
6.
J Virus Erad ; 9(3): 100345, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37753336

RESUMO

Introduction: Antiretroviral therapy for people living with HIV-1 must be taken lifelong due to the persistence of latent virus in long-lived and proliferating CD4+ T cells. Vitamin D3 is a steroidal gene transcription regulator which exerts diverse effects on immune and epithelial cells including reductions in CD4+ T cell proliferation and improvement in gut barrier integrity. We hypothesised that a high dose of vitamin D3 would reduce the size of the HIV-1 reservoir by reducing CD4+ T cell proliferation. Methods: We performed a randomised placebo-controlled trial evaluating the effect of 24 weeks of vitamin D3 (10,000 international units per day) on the HIV-1 reservoir and immunologic parameters in 30 adults on antiretroviral therapy; participants were followed for 12 weeks post-treatment. The primary endpoint was the effect on total HIV-1 DNA at week 24. Parameters were assessed using mixed-effects models. Results: We found no effect of vitamin D3 on the change in total HIV-1 DNA from week 0 to week 24 relative to placebo. There were also no changes in integrated HIV-1 DNA, 2-long-terminal repeat (2-LTR) circles or cell-associated HIV-1 RNA. Vitamin D3 induced a significant increase in the proportion of central memory CD4+ and CD8+ T cells, a reduction in the proportion of senescent CD8+ T cells and a reduction in the natural killer cell frequency at all time points including week 36, 12 weeks after the study drug cessation. At week 36, there was a significant reduction in total HIV-1 DNA relative to placebo and persistently elevated 25-hydroxyvitamin D levels. No significant safety issues were identified. Conclusions: Vitamin D3 administration had a significant impact on the T cell differentiation but overall effects on the HIV-1 reservoir were limited and a reduction in HIV-1 DNA was only seen following cessation of the study drug. Additional studies are required to determine whether the dose and duration of vitamin D3 can be optimised to promote a continued depletion of the HIV-1 reservoir over time. Trial registration: ClinicalTrials.gov NCT03426592.

7.
Med J Aust ; 196(5): 332-6, 2012 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-22432672

RESUMO

OBJECTIVES: To determine incidence and trends in antibiotic resistance in Australian Salmonella enterica subspecies enterica serovars Typhi (S. Typhi) and Paratyphi (S. Paratyphi) isolates over the past 26 years. DESIGN: A retrospective analysis of consecutive microbiologically confirmed enteric fever isolates. PARTICIPANTS AND SETTING: All S. Typhi and S. Paratyphi isolates from patients diagnosed with enteric fever in Australia between 1985 and 2010. MAIN OUTCOME MEASURES: Incidence and variation in antibiotic resistance over time and according to country of origin. RESULTS: We analysed 2551 isolates, which originated from 74 countries or regions, mainly India (33%) and Indonesia (22%). The incidence among Australian residents increased from four to five before 2003 to seven cases per million person-years after 2003. Multidrug resistance (chloramphenicol, ampicillin, trimethoprim) and nalidixic acid resistance emerged rapidly from the early 1990s, with nalidixic acid resistance increasing to 70% in 2009-2010, while multidrug resistance was relatively stable at between 4% and 11%. Nalidixic acid and multidrug resistance rates are highest in isolates from the Indian subcontinent. Some countries in South-East Asia, such as Indonesia, had very low rates of resistance; however, this varied across the region. CONCLUSIONS: Nalidixic acid resistance has become widespread in enteric fever isolates from the Indian subcontinent and some parts of South-East Asia, justifying the use of ceftriaxone or azithromycin rather than ciprofloxacin as first-line treatment. However, resistance in some countries remains rare, potentially allowing treatment to be adjusted according to country of origin.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sudeste Asiático , Austrália/epidemiologia , Criança , Pré-Escolar , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ácido Nalidíxico/farmacologia , Estudos Retrospectivos , Salmonella typhi/isolamento & purificação , Febre Tifoide/epidemiologia , Adulto Jovem
8.
Open Forum Infect Dis ; 6(7)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31363769

RESUMO

The diagnosis of central nervous system (CNS) infection relies upon analysis of cerebrospinal fluid (CSF). We present 4 cases of CNS infections associated with basal meningitis and hydrocephalus with normal ventricular CSF but grossly abnormal lumbar CSF. We discuss CSF ventricular-lumbar composition gradients and putative pathophysiological mechanisms and highlight clinical clues for clinicians.

9.
Tuberculosis (Edinb) ; 114: 91-102, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30711163

RESUMO

OBJECTIVE: Accurate and timely diagnosis of tuberculosis (TB) is essential to control the global pandemic. Currently available immunodiagnostic tests cannot discriminate between latent tuberculosis infection (LTBI) and active tuberculosis. This study aimed to determine whether candidate mycobacterial antigen-stimulated cytokine biomarkers can discriminate between TB-uninfected and TB-infected adults, and additionally between LTBI and active TB disease. METHODS: 193 adults were recruited, and categorised into four unambiguous diagnostic groups: microbiologically-proven active TB, LTBI, sick controls (non-TB lower respiratory tract infections) and healthy controls. Whole blood assays were used to determine mycobacterial antigen (CFP-10, ESAT-6, PPD)-stimulated cytokine (IL-1ra, IL-2, IL-10, IL-13, TNF-α, IFN-γ, IP-10 and MIP-1ß) responses, measured by Luminex multiplex immunoassay. RESULTS: The background-corrected mycobacterial antigen-stimulated cytokine responses of all eight cytokines were significantly higher in TB-infected participants compared with TB-uninfected individuals, with IL-2 showing the best performance characteristics. In addition, mycobacterial antigen-stimulated responses with IL-1ra, IL-10 and TNF-α were higher in participants with active TB compared those with LTBI, reaching statistical significance with PPD stimulation, although there was a degree of overlap between the two groups. CONCLUSION: Mycobacterial antigen-stimulated cytokine responses may prove useful in future immunodiagnostic tests to discriminate between tuberculosis-infected and tuberculosis-uninfected individual, and potentially between LTBI and active tuberculosis.


Assuntos
Citocinas/sangue , Tuberculose/diagnóstico , Adulto , Antígenos de Bactérias/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Citocinas/biossíntese , Diagnóstico Diferencial , Feminino , Humanos , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Masculino , Pessoa de Meia-Idade , Curva ROC , Teste Tuberculínico/métodos , Adulto Jovem
10.
BMC Med Inform Decis Mak ; 8: 35, 2008 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-18667084

RESUMO

BACKGROUND: The ideal method to encourage uptake of clinical guidelines in hospitals is not known. Several strategies have been suggested. This study evaluates the impact of academic detailing and a computerised decision support system (CDSS) on clinicians' prescribing behaviour for patients with community acquired pneumonia (CAP). METHODS: The management of all patients presenting to the emergency department over three successive time periods was evaluated; the baseline, academic detailing and CDSS periods. The rate of empiric antibiotic prescribing that was concordant with recommendations was studied over time comparing pre and post periods and using an interrupted time series analysis. RESULTS: The odds ratio for concordant therapy in the academic detailing period, after adjustment for age, illness severity and suspicion of aspiration, compared with the baseline period was OR = 2.79 [1.88, 4.14], p < 0.01, and for the computerised decision support period compared to the academic detailing period was OR = 1.99 [1.07, 3.69], p = 0.02. During the first months of the computerised decision support period an improvement in the appropriateness of antibiotic prescribing was demonstrated, which was greater than that expected to have occurred with time and academic detailing alone, based on predictions from a binary logistic model. CONCLUSION: Deployment of a computerised decision support system was associated with an early improvement in antibiotic prescribing practices which was greater than the changes seen with academic detailing. The sustainability of this intervention requires further evaluation.


Assuntos
Antibacterianos/uso terapêutico , Sistemas de Apoio a Decisões Clínicas , Quimioterapia Assistida por Computador , Pneumonia/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Estudos de Coortes , Infecções Comunitárias Adquiridas/tratamento farmacológico , Serviços Médicos de Emergência , Feminino , Fidelidade a Diretrizes , Hospitais de Ensino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto
11.
Tuberc Res Treat ; 2018: 6860479, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30057812

RESUMO

Setting. Tuberculosis treatment requires long regimens with multiple antibiotics and is complicated by antibiotic resistance and intolerance. Fluoroquinolones were introduced for the treatment of multidrug resistant TB and have become a vital part of therapy. Objective. Reviewing the indications for fluoroquinolones use in the treatment of active TB in Victoria, Australia. Design. This was a retrospective case-control study of Victorian patients prescribed fluoroquinolones for active tuberculosis, from January 2011 to December 2016. Indications for fluoroquinolone use were extracted from an existing public health database. Results. There were 2268 patients notified to have tuberculosis in Victoria between 2011 and 2016, 276 (12.2%) of whom received a fluoroquinolone. The indications were substitution when intolerance was present (33.3%) or anticipated (21.0%), proven drug resistance (22.5%), suspected drug resistance (13.0%), and site of disease (10.1%). Where fluoroquinolones were prescribed for suspected drug resistance, only a minority of isolates (13%) had resistance confirmed. Conclusion. Fluoroquinolones were most commonly used as replacement for first-line therapy related to adverse effects, when either present or anticipated. Where fluoroquinolones were prescribed for suspected drug resistance, only a minority of isolates ultimately had resistance confirmed. These findings reinforce the importance of fluoroquinolones in TB therapy and the need for ongoing pharmacovigilance to ensure appropriate use.

13.
Emerg Med Australas ; 19(5): 418-26, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17919214

RESUMO

OBJECTIVE: To identify independent predictors of severe pneumonia in a local population, and create a simple severity score that would be useful in the ED. METHODS: Data on the clinical features of patients presenting to hospital with community-acquired pneumonia were collected. Multivariate logistic regression was used to identify independent predictors of death, requirement for ventilatory or inotropic support, and these combined. These predictors were used to modify an existing severity score, and its performance was tested in a second cohort of patients. RESULTS: A total of 392 patients in the derivation, and 330 in the validation cohorts. Independent predictors of 'death and/or requirement for ventilatory or inotropic support' were: systolic blood pressure (BP) <90 mmHg (OR 3.49 [95% CI 1.12-10.38]); acute confusion (OR 5.48 [95% CI 2.74-10.99]); oxygen saturations < or =90% (OR 3.49 [95% CI 1.77-6.89]); and respiratory rate > or =30/min (OR 2.65 [95% CI 1.35-5.21]). Age >65 years was not an independent predictor in this patient group (OR 0.52 [95% CI 0.23-1.16]). This information was used to propose that severe pneumonia could be predicted by two or more of: acute confusion; oxygen saturations < or =90%; respiratory rate > or =30/min; and either systolic BP <90 mmHg; or diastolic BP < or =60 mmHg. In a separate cohort, the performance of this score was similar to other tools. CONCLUSION: This provides a practical tool that can be used to 'flag' impending patient demise. Its advantages are that it is simple, uses predictive variables, does not require invasive testing, and removes bias regarding patient age. Like other tools, its accuracy is not perfect, and it should only be used to augment clinical judgement.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Pneumonia Bacteriana/diagnóstico , Resultado do Tratamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/fisiopatologia , Confusão , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/fisiopatologia , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença
14.
J Infect ; 75(2): 132-145, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28483404

RESUMO

OBJECTIVES: A biomarker indicating successful tuberculosis (TB) therapy would assist in determining appropriate length of treatment. This study aimed to determine changes in mycobacteria-specific antigen-induced cytokine biomarkers in patients receiving therapy for latent or active TB, to identify biomarkers potentially correlating with treatment success. METHODS: A total of 33 adults with active TB and 36 with latent TB were followed longitudinally over therapy. Whole blood stimulation assays using mycobacteria-specific antigens (CFP-10, ESAT-6, PPD) were done on samples obtained at 0, 1, 3, 6 and 9 months. Cytokine responses (IFN-γ, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1ß, and TNF-α) in supernatants were measured by Luminex xMAP immunoassay. RESULTS: In active TB cases, median IL-1ra (with CFP-10 and with PPD stimulation), IP-10 (CFP-10, ESAT-6), MIP-1ß (ESAT-6, PPD), and TNF-α (ESAT-6) responses declined significantly over the course of therapy. In latent TB cases, median IL-1ra (CFP-10, ESAT-6, PPD), IL-2 (CFP-10, ESAT-6), and IP-10 (CFP-10, ESAT-6) responses declined significantly. CONCLUSIONS: Mycobacteria-specific cytokine responses change significantly over the course of therapy, and their kinetics in active TB differ from those observed in latent TB. In particular, mycobacteria-specific IL-1ra responses are potential correlates of successful therapy in both active and latent TB.


Assuntos
Antígenos de Bactérias/imunologia , Citocinas/sangue , Citocinas/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/tratamento farmacológico , Tuberculose/imunologia , Adolescente , Adulto , Antituberculosos/uso terapêutico , Biomarcadores/sangue , Estudos de Coortes , Monitoramento de Medicamentos , Feminino , Humanos , Tuberculose Latente , Masculino , Pessoa de Meia-Idade , Tuberculose/classificação , Tuberculose/diagnóstico , Adulto Jovem
16.
Tuberculosis (Edinb) ; 95(3): 217-28, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25797612

RESUMO

The ability to monitor response to therapy for tuberculosis (TB) and confirm adequate treatment would be a major advance. The low reversion rate of interferon-gamma based assays means that they are unlikely to be useful for monitoring therapy. Several exploratory studies have evaluated the diagnostic potential of cytokine biomarkers other than interferon-gamma for monitoring anti-tuberculous therapy. A systematic review of these studies was performed to identify the most promising candidate biomarkers. TNF-α, IL-2, IL-6, IL-10 and IL-12 were the most extensively investigated cytokines. There was significant heterogeneity between studies in relation to study design and laboratory methodology, complicating direct comparisons. There was marked variation between studies in the observed changes during treatment for many of the biomarkers. Further longitudinal studies in sufficiently large patient cohorts with rigorous methodology are needed to determine the true potential of individual cytokine biomarkers, or combinations, for monitoring TB treatment.


Assuntos
Antituberculosos/uso terapêutico , Citocinas/sangue , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Biomarcadores/sangue , Humanos , Mycobacterium tuberculosis/imunologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Resultado do Tratamento , Tuberculose/sangue , Tuberculose/diagnóstico , Tuberculose/imunologia , Tuberculose/microbiologia
17.
Tuberculosis (Edinb) ; 95(3): 343-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25837441

RESUMO

INTRODUCTION: The ability to monitor and confirm adequate treatment of latent TB infection (LTBI) would be a major advance. The potential immunomodulatory effects of anti-tuberculous drugs and steroids need to be considered in assessing the utility of cytokine-based assays for this purpose. METHODS: We determined whether anti-tuberculous antibiotics or dexamethasone affect the production of IFN-γ and other potential cytokine biomarkers (TNF-α, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1ß) in the QuantiFERON-TB Gold In-Tube (QFT-IT) assay. Blood from ten adults with LTBI was added to one standard set of QFT-IT tubes and five further sets containing therapeutic concentrations of either isoniazid, rifampicin, isoniazid and rifampicin, ciprofloxacin or dexamethasone. Resulting supernatants were analysed by ELISA (QFT-IT assay IFN-γ) and xMAP-Luminex assays (all cytokines). RESULTS: Anti-tuberculous antibiotics had only a limited effect on categorical QFT-IT assay results and the production of cytokines. In contrast, dexamethasone resulted in a change in categorical results from positive to negative in four of ten patients, and caused a marked reduction in IL-13 and IL-1ra responses. CONCLUSION: Substantial changes in TB-antigen-induced IFN-γ and other cytokine responses during treatment likely primarily reflect host immunological changes rather than immunomodulatory effects of anti-tuberculous antibiotics. Results from cytokine-based assays in patients on corticosteroids should be interpreted with caution.


Assuntos
Corticosteroides/uso terapêutico , Antibióticos Antituberculose/uso terapêutico , Citocinas/sangue , Dexametasona/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Testes de Liberação de Interferon-gama , Tuberculose Latente/tratamento farmacológico , Adulto , Biomarcadores/sangue , Feminino , Humanos , Interferon gama/sangue , Tuberculose Latente/sangue , Tuberculose Latente/diagnóstico , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Masculino , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
18.
PLoS One ; 10(5): e0127726, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26011034

RESUMO

BACKGROUND: Understanding retention and loss to follow up in HIV care, in particular the number of people with unknown outcomes, is critical to maximise the benefits of antiretroviral therapy. Individual-level data are not available for these outcomes in Australia, which has an HIV epidemic predominantly focused amongst men who have sex with men. METHODS AND FINDINGS: A network of the 6 main HIV clinical care sites was established in the state of Victoria, Australia. Individuals who had accessed care at these sites between February 2011 and June 2013 as assessed by HIV viral load testing but not accessed care between June 2013 and February 2014 were considered individuals with potentially unknown outcomes. For this group an intervention combining cross-referencing of clinical data between sites and phone tracing individuals with unknown outcomes was performed. 4966 people were in care in the network and before the intervention estimates of retention ranged from 85.9%-95.8% and the proportion with unknown outcomes ranged from 1.3-5.5%. After the intervention retention increased to 91.4-98.8% and unknown outcomes decreased to 0.1-2.4% (p<.01 for all sites for both outcomes). Most common reasons for disengagement from care were being too busy to attend or feeling well. For those with unknown outcomes prior to the intervention documented active psychiatric illness at last visit was associated with not re-entering care (p = 0.04). CONCLUSIONS: The network demonstrated low numbers of people with unknown outcomes and high levels of retention in care. Increased levels of retention in care and reductions in unknown outcomes identified after the intervention largely reflected confirmation of clinic transfers while a smaller number were successfully re-engaged in care. Factors associated with disengagement from care were identified. Systems to monitor patient retention, care transfer and minimize disengagement will maximise individual and population-level outcomes for populations with HIV.


Assuntos
Redes Comunitárias/estatística & dados numéricos , Atenção à Saúde/métodos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Cooperação do Paciente , Atenção à Saúde/estatística & dados numéricos , Infecções por HIV/diagnóstico , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Vitória/epidemiologia , Carga Viral
19.
AIDS Res Hum Retroviruses ; 20(12): 1364-7, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15650430

RESUMO

The proportion of human immunodeficiency virus type 1 (HIV-1) among Vietnamese injecting drug users (IDUs) in Melbourne, Australia exceeds that of the background population. To investigate the molecular epidemiology of HIV-1 among this group, the C2-V4 region of the HIV-1 envelope was directly sequenced from 11 Vietnamese Australians and 19 non-Vietnamese Australian controls. A significant difference in the distribution of the HIV-1 subtypes was demonstrated, with greater than 50% of Vietnamese Australian IDU shown to be infected with CRF01_AE-the predominant subtype in Southeast Asia, rather than subtype B, which dominates the Australian epidemic and which was found in 89.5% of the non-Vietnamese controls. The genetic diversity of the CRF01_AE epidemic in Vietnamese Australian IDUs was substantially lower that that of the background subtype B, consistent with a more recent introduction of a limited number of viral strains from Vietnam. These results support public health policy targeting Australian IDUs of Vietnamese ethnicity as a distinct vulnerable population.


Assuntos
Infecções por HIV/epidemiologia , HIV-1/genética , Abuso de Substâncias por Via Intravenosa/virologia , Austrália/epidemiologia , Etnicidade , Genes env/genética , Infecções por HIV/complicações , Infecções por HIV/etnologia , Infecções por HIV/transmissão , HIV-1/classificação , Humanos , Dados de Sequência Molecular , Filogenia , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Vietnã/etnologia
20.
J Clin Virol ; 26(2): 133-42, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12600645

RESUMO

BACKGROUND: The movement of people with their constructed identities including ethnicity has always been one of the determinants of the human immunodeficiency virus (HIV) pandemic. An example of the contributions of travel and ethnicity to experiences of HIV can be seen in the Vietnamese community in Australia. OBJECTIVES: This paper seeks to describe the contributions of ethnicity and travel to the Australian HIV epidemic with particular reference to the evolving epidemic within the Vietnamese Australian community. STUDY DESIGN: We reviewed the available data on the HIV epidemic in Australia with reference to overseas acquisition, ethnicity, the epidemic in the Vietnamese community and the determinants of the current patterns of transmission within this community. RESULTS: Available data suggests that 20-25% of HIV infections notified in Australia are acquired overseas. This proportion is higher in some specific categories such as heterosexually acquired infections. Notification rates are no higher in Vietnamese Australians than in the general Australian population apart from infections associated with injecting drug use (IDU) notified in the state of Victoria. The reasons for this increased rate of notification include increased vulnerability to blood borne virus infection in Australia and the additional, unique risk of frequent travel to Vietnam, a country where IDU carries a high risk of HIV infection. CONCLUSIONS: Australia has succeeded in stabilising the HIV epidemic partly through successful interventions to limit the spread of infection among IDUs. There is now early evidence that HIV transmission may be increasing amongst Vietnamese Australian IDUs. Timely responses that help Vietnamese Australian IDUs reduce their accumulation of risk are likely to be important in determining the level of harm associated with IDU throughout Australia.


Assuntos
Infecções por HIV/epidemiologia , Austrália/epidemiologia , Etnicidade , Feminino , Infecções por HIV/complicações , Infecções por HIV/transmissão , Humanos , Masculino , Fatores de Risco , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Viagem , Vietnã/etnologia
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